A pharmaco-EEG-based assessment of the interaction between ethanol and zonisamide

Abstract

Aims: Recent research suggests a potential role for a new generation of anticonvulsant drugs, including zonisamide, in the treatment of alcohol dependence. Some elements of the central mechanism of action that zonisamide has in common with ethanol, give rise to the question of whether there is an interaction between these two agents and whether there is any risk associated with the enhanced depressive effect of these agents on the central nervous system. Methods: This study uses a pharmaco-EEG method to examine the interaction of ethanol with zonisamide. The influence of zonisamide on the effect of ethanol on EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex) was determined. Zonisamide was administered p.o. as a single dose (20 or 60 mg/kg) or repeatedly at a dose of 30 mg/kg/day for 14 days. Ethanol was injected i.v. at a dose of 0.8 g/kg 180 min after the administration of zonisamide. Results: Ethanol caused an increase in the low frequencies (0.5-4 Hz) in the recording, as well as a marked decrease in the higher frequencies (13-30 and 30-45 Hz). Changes in the EEG recordings after zonisamide alone were more significant compared with these after repeated doses. In the hippocampus after single dose of drug the proportion of the low frequency (0.5-4 Hz) increased, whereas the proportion of high frequencies decreased. Combined administration of ethanol and zonisamide (60 mg/kg) resulted in a markedly synergistic effect in the examined structures. A beneficial effect of repeatedly administered zonisamide on ethanol-induced EEG changes was observed, especially in the hippocampus. Conclusion: Zonisamide in repeated doses decreases the sensitivity of the hippocampus to ethanol, an observation that may be important in the treatment of alcohol addiction. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.